Commencement of pharmacotherapy

• The GDG acknowledged that a two-week trial of diet and physical activity to achieve glycaemic control is typically conducted before considering commencement of blood glucose-lowering medication for GDM. The trials comparing different pharmacological agents included in the systematic review used a range of lengths of diet/activity (when described this ranged from 3 to 28 days, most commonly seven days). However, in some settings and for some clinical presentations (e.g. based on level of glycaemic control or maternal/fetal concerns), medication may be commenced without a trial of diet/activity. Trigger for treatment initiation or change
• In the trials comparing different pharmacological agents included in the systematic review, thresholds used for insulin initiation, treatment agent switch and dose escalation were poorly and inconsistently reported. In most studies, the trigger for FPG was 5.0 to 5.5 mmol/L (90 to 100 mg/dL), with some using stricter (3.4 to 5.0 mmol/L [60 to 90 mg/dL]) or looser (<6.1 mmol/L [<110 mg/dL]) targets. One-hour postprandial targets ranged from <6.5 to <9.0 mmol/L (<117 to <162 mg/dL) and most studies used a twohour postprandial target of <6.7 mmol/L (120 mg/dL), ranging between <5.6 and <7.8 mmol/L (<100 mg/dL and <140 mg/dL).
• In clinical practice, a flexible approach may be appropriate and triggers for treatment initiation or change will likely be based on a woman’s blood glucose control and clinical criteria that reflect local realities (e.g. food insecurity, challenges in monitoring or follow-up), aiming to balance safety and feasibility. Choice of glucose-lowering agent
• The GDG acknowledged that although there is some indication of possible benefits of commencing with metformin, overall the evidence does not strongly support metformin over insulin as a first-line medicine. Many women who begin pharmacotherapy with metformin will go on to need insulin. Clinical practices and the availability of medications are highly variable. The choice of glucose-lowering agent for women with GDM will be based on the woman’s glycaemic control, local availability and expertise, and her values and preferences.
• Many blood-glucose lowering agents are either not recommended for use in pregnancy or do not have adequate safety data in pregnancy (e.g. GLP-1Ras and SGLT2 inhibitors). However, the GDG acknowledged that there may be situations where a blood-glucose lowering agent other than insulin or metformin needs to be considered (e.g. when a woman refuses insulin and metformin is not tolerated or is ineffective in achieving the woman’s glycaemic control). In these circumstances other agents, such as a sulfonylurea, may be considered after discussion of potential benefits and harms. Dosage of glucose-lowering agent
• Titration of medications for glycaemic control is individualized and guided by regular blood glucose monitoring. Stopping treatment with glucose-lowering agents
• The GDG acknowledged that usual clinical practice is to stop treatment with glucose-lowering agents soon after the birth of the baby. Due to the increased risk of type 2 diabetes in women who have experienced GDM (7), follow-up assessment of glucose tolerance is essential 6 to 12 weeks postnatally.